Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3-green fluorescent protein reporter mice

Research Project

Project/Area Number	25870039
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Orthopaedic surgery Laboratory animal science
Research Institution	Tohoku University
Principal Investigator	MORI Yu 東北大学, 大学病院, 助教 (70634541)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	骨折修復機構 / 間葉系幹細胞 / Dickkopf 3 / 血管新生 / Dckkopf3 / Dickkopf3
Outline of Final Research Achievements	Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic and angiogenic differentiation. Here, we demonstrate Dickkopf-related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein (Dkk3-GFP) reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells with and smooth muscle alpha actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 had disappeared in the late phase of fracture healing except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen-positive blood vessels and the related avascular tissue.